Dose measurement system and method

ABSTRACT

Embodiments described herein generally relate to devices, systems and methods for measuring the dose remaining in a drug delivery device that is used for delivering a dose to a patient. In some embodiments, a dose measurement system for measuring the liquid volume in a container includes a plurality of light sources which are disposed and configured to emit electromagnetic radiation toward the container. A plurality of sensors are located in the apparatus that are optically coupleable to the plurality of light sources and are disposed and configured to detect the electromagnetic radiation emitted by at least a portion of the light sources. The apparatus also includes a processing unit configured to receive data representing the portion of the detected electromagnetic radiation from each of the plurality of sensors. The processing unit is further operable to convert the received data into a signature representative of the electromagnetic radiation detected by the plurality of sensors.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of and claims priority to U.S. patentapplication Ser. No. 14/548,679, filed Nov. 20, 2014, entitled “DoseMeasurement System and Method,” now U.S. Pat. No. 9,255,830, which is acontinuation of International Patent Application No. PCT/US2013/041982,filed May 21, 2013, entitled “Dose Measurement System and Method,” whichis a continuation-in-part of U.S. patent application Ser. No.13/796,889, filed Mar. 12, 2013, now U.S. Pat. No. 8,817,258, entitled“Dose Measurement System and Method,” which claims priority to and thebenefit of U.S. Provisional Application No. 61/754,262, filed Jan. 18,2013, entitled “Non-Invasive Injection Pen and Syringe Sensor Device,”and U.S. Provisional Application No. 61/649,919, filed May 21, 2012,entitled “Non-Invasive Injection Pen and Syringe Sensor Device,” all ofwhich are hereby incorporated by reference in their entirety.

This application also claims priority to and the benefit of U.S.Provisional Application No. 61/754,262, filed Jan. 18, 2013, entitled“Non-Invasive Injection Pen and Syringe Sensor Device,” the disclosureof which is hereby incorporated by reference in its entirety.

This application also claims priority to and the benefit of U.S.Provisional Application No. 61/649,919, filed May 21, 2012, entitled“Non-Invasive Injection Pen and Syringe Sensor Device,” the disclosureof which is hereby incorporated by reference in its entirety.

BACKGROUND

Embodiments described herein relate generally to devices, systems andmethods for measuring the dose remaining in a drug delivery device.

Many chronic disease patients are prescribed medications that need to beself administered using injection pens or similar drug delivery devices.For example, patients diagnosed with Type I or II diabetes need toregularly check their blood glucose levels and self administer anappropriate dose of insulin using an injection pen. In order to monitorthe efficacy of the medication, dose information needs to be recorded.The process of manually logging dose information, particularly in anuncontrolled setting, is tedious and error prone. Patients often forgetto log the dose information when administering medicine. In addition,many such patients can be minors or elderly and cannot efficiently keeptrack of the dose information.

Incomplete dosage records hinder the ability of the patient toself-manage disease conditions and prevent caretakers from adjustingcare plans through behavioral insight. Lack of adherence to targetdosage schedules for injectable medicine can result in an increased needfor critical care, which results in a significant increase in healthcare costs in countries around the world.

Thus, there is a need for better technological aids to assist patientsin improving their ability to self-manage disease treatment. Such aidscan not only make the patients more aware and educated about theirhealth condition, but also assist caregivers in better monitoringpatient health. In particular, there is a need for systems, devices andmethods that facilitate data acquisition on patient behavior and thatallow that data to be used to reduce the incidence of hospital visits(e.g., readmission), as well as to inform and educate patients, careproviders, family and financial service providers.

SUMMARY

Embodiments described herein relate generally to devices, systems andmethods for measuring the dose remaining in a drug delivery device. Insome embodiments, a dose measurement system for measuring the liquidvolume in a container includes a plurality of light sources which aredisposed and configured to emit electromagnetic radiation toward thecontainer. A plurality of sensors are optically coupleable to theplurality of light sources and are disposed and configured to detect theelectromagnetic radiation emitted by at least a portion of the lightsources. The apparatus also includes a processing unit configured toreceive data representing the portion of the detected electromagneticradiation from each of the plurality of sensors and to convert thereceived data into a signature representative of the electromagneticradiation detected by the plurality of sensors.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic block diagram of a dose measurement system,according to an embodiment.

FIG. 2 is a perspective view of a dose measurement system, according toan embodiment.

FIG. 3 is an exploded perspective view of the dose measurement system ofFIG. 2.

FIG. 4 is a top exploded top view of the dose measurement system of FIG.2.

FIG. 5 is a schematic illustration of a communications interface thatcan be included in the dose measurement system of FIG. 2, according toan embodiment.

FIG. 6 is a schematic ray diagram of different modes of lighttransmission between a first medium and a second medium.

FIG. 7 is a cross-section view of a dose measurement system, accordingto an embodiment.

FIG. 8 is a cross-section view of a dose measurement system, accordingto an embodiment.

FIG. 9 is a cross-section view of a dose measurement system, accordingto an embodiment.

FIG. 10 is a side cross-section view of a dose measurement system,according to an embodiment.

FIG. 11A-11C are cross-section views of an embodiment of a dosemeasurement system, in a first, second and third configuration,respectively.

FIG. 12 is a cross-section view of the dose measurement system of FIG.11A taken along line A-A.

FIG. 13 is a cross-section view of the dose measurement system of FIG.11C taken along line B-B.

FIG. 14 shows reference signature signals of sensors of a dosemeasurement system, according to an embodiment.

FIG. 15 is a flow diagram of a method of operation of the dosemeasurement system, according to an embodiment.

FIG. 16 is a flow diagram of a method of operation of the dosemeasurement system, according to an embodiment.

FIG. 17 is a schematic block diagram of a health management systemassociated with a dose measurement system, according to an embodiment.

DETAILED DESCRIPTION

Embodiments described herein relate generally to devices, systems andmethods for measuring the dose remaining in a drug delivery device. Insome embodiments, a dose measurement system for measuring the liquidvolume in a container includes a plurality of light sources which aredisposed and configured to emit electromagnetic radiation toward thecontainer. A plurality of sensors are optically coupleable to theplurality of light sources and are disposed and configured to detect theelectromagnetic radiation emitted by at least a portion of the lightsources. The apparatus also includes a processing unit configured toreceive data representing the portion of the detected electromagneticradiation from each of the plurality of sensors and to convert thereceived data into a signature representative of the electromagneticradiation detected by the plurality of sensors.

In some embodiments, a method of estimating a volume of liquid in a drugdelivery device includes causing a plurality of light sources to emitelectromagnetic radiation toward a drug container and detecting asignature of the emitted electromagnetic radiation through the drugcontainer with a plurality of sensors. The detected signature is thencompared to a plurality of reference signatures to determine the volumeof liquid in the drug container. Each of the plurality of referencesignatures correspond to a volume level remaining in the drug container.In some embodiments, detecting the signature of the emittedelectromagnetic radiation through the drug container includes detectingat least a portion of the electromagnetic radiation emitted from atleast a portion of the plurality of light sources. The portion of theelectromagnetic radiation detected by each of the plurality of sensordevices can be compiled into the signal signature.

In some embodiments, the method also includes calculating a dosedelivered to a patient based on the volume of liquid in the drugcontainer. In some embodiments, the dose delivered to a patient iscompared with a patient medication schedule to monitor compliance. Themethod can further include correcting the signal signature forbackground light which can contribute to noise. The correction caninclude comparing the signal signature with a background signaturedetected by the plurality of sensors in a dark state of each of theplurality of light sources. In some embodiments, the method alsoincludes generating the plurality of reference signatures by recordingthe signature for a range of dose volumes in the drug container. Themethod can also include associating the signal with the referencesignature using probabilistic matching to determine the volume of liquidremaining in the dose container.

In some embodiments, a method for determining a dose delivered by aninjection pen using the drug measurement system includes causing aplurality of light sources to emit electromagnetic radiation toward theinjection pen a first time and detecting a first signature of theemitted electromagnetic radiation through the injection pen with aplurality of sensors. The first signature is then compared to aplurality of reference signatures to determine the first volume ofliquid in the injection pen. The method further includes causing theplurality of light sources to emit electromagnetic radiation toward theinjection pen a second time, after the first time, and detecting asecond signature of the emitted electromagnetic radiation through theinjection pen with the plurality of sensors. The second signature isthen compared to the plurality of reference signatures to determine thesecond volume of liquid in the injection pen. The second volume can bededucted from the first volume to determine a dose delivered from theinjection pen.

In some embodiments, the plurality of light sources and the plurality ofsensor are disposed in an injection pen cap. In some embodiments, themethod includes detecting the first signature prior to the injection pencap being removed from the injection pen and detecting the secondsignature after the injection pen cap has been placed back on theinjection pen. The method can also include communicating the dosedelivered information to an external device. In some embodiments, themethod includes switching the pen cap to a power save mode after apredetermined period of inactivity of the pen cap. In some embodiments,the method further includes alerting the user if a volume of liquidremaining in the drug container is critically low and/or if it is timeto deliver a dose of medication.

In some embodiments, a health management system includes a drug deliverydevice including a drug reservoir, and a dose measurement systemconfigured to be removably coupleable to the drug delivery device. Thedose measurement system includes a plurality of light sources disposedand configured to emit electromagnetic radiation toward the drugreservoir a plurality of sensors optically coupleable to the pluralityof light sources disposed and configured to detect a quantity ofelectromagnetic radiation communicated through the drug reservoir. Thequantity of electromagnetic radiation serves as a signaturerepresentative of the volume of liquid remaining in the drug reservoir.The health management system also includes a display configured topresent information to a user indicative of the volume of liquidremaining in the drug reservoir. The dose measurement system can beconfigured to communicate data representative of the volume of liquidremaining in the drug reservoir to a remote device, for example, toallow the remote device to calculate a dose delivered to the patient. Insome embodiments, the dose management system is configured to receiveuser health data from the remote device which can include, for exampleuser blood glucose level, user diet, user exercise, and/or user homehealth monitored data.

As used in this specification, the terms “about” and “approximately”generally include plus or minus 10% of the value stated. For example,about 5 would include 4.5 to 5.5, approximately 10 would include 9 to11, and about 100 would include 90 to 110.

FIG. 1 is a schematic block diagram of a dose measurement system 100 formeasuring the dose in a drug delivery device 110. The dose measurementsystem 100 includes a lighting module 140, a sensing module 150, aprocessing unit 160 and a communications module 170. The dosemeasurement system 100 can be configured to be removably coupleable tothe drug delivery device 110 that is used to deliver a drug dose to atarget T such as, for example, a human patient.

The drug delivery device 110 can be any drug delivery device 110 thatcan be used for injecting a medication into a patient. For example, thedrug delivery device 110 can be an injection pen (e.g., insulininjection pen), a syringe, pump (e.g., insulin delivery pump), anampoule, or a vial. The dose measurement system 100 can be configured tobe coupleable to a wide variety of drug delivery devices 110, e.g.,different shapes, sizes, and drug volumes. In some embodiments, the dosemeasurement system 100 can be configured to receive a portion of thedrug delivery device 110, e.g., a portion that defines an internalvolume containing the drug, an injector, and/or plunger. In someembodiments, the dose measurement system 100 is configured to beremovable from the drug delivery device 110 when the user is deliveringa dose to the target T. In some embodiments, the dose measurement system110 can remain attached to the drug delivery device 110 when the user isdelivering a dose to the target T. In some embodiments, the dosemeasurement system 100 is configured to be reusable. In someembodiments, the dose measurement system 110 can be permanently coupledto the drug delivery device 110, for example, integrated into the bodyof the drug delivery device. In such embodiments, the dose measurementsystem 100 can be disposable.

The lighting module 140 includes a plurality of light sources configuredto emit electromagnetic radiation towards the drug delivery device 110.In some embodiments, the plurality of light sources can be configured toemit electromagnetic radiation towards a drug reservoir (not shown) ofthe drug delivery device 110. In some embodiments, each of the pluralityof light sources can be a light emitting diode (LED). In someembodiments, the plurality of light sources can be configured to emitinfrared radiation or microwave radiation, such that the electromagneticradiation can penetrate through a housing and any internal components ofthe drug delivery device 110, and/or the liquid drug contained therein.In some embodiments, the plurality of light sources can be configured toemit continuous electromagnetic radiation for a predefined time period.In some embodiments, the plurality of light sources can be configured toemit pulses of electromagnetic radiation, e.g., a series of less than100 microsecond pulses.

The sensing module 150 includes a plurality of sensors that areoptically coupleable to the plurality of light sources of the lightingmodule 140. In some embodiments, the each of the plurality of sensorscan be a photodetector. The plurality of sensors are disposed andconfigured to detect the electromagnetic radiation emitted by at least aportion of the light sources. In some embodiments, the detectedelectromagnetic radiation includes transmitted, refracted and reflectedportions of the electromagnetic radiation. In some embodiments, therefracted electromagnetic radiation can include multi-directionalrefraction caused by a lensing effect of a curved surface of the housingof the drug delivery device 110 and/or the drug reservoir.

The processing unit 160 is configured to receive the electromagneticradiation signal from the sensing module 150 (i.e., each of theplurality of sensors) and convert the received data into a signalsignature representative of the electromagnetic radiation detected byeach of the plurality of sensors. The processing unit 160 can include aprocessor, e.g., a microcontroller, a microprocessor, an ASIC chip, anARM chip, an analog to digital convertor (ADC), or a programmable logiccontroller (PLC). In some embodiments, the processing unit 160 caninclude a memory that is configured to temporarily store at least one ofthe electromagnetic radiation data detected by each of the plurality ofsensors and the signal signature produced from it. In some embodiments,the memory can also be configured to store a plurality of referencesignatures. Each of the plurality of reference signatures can berepresentative of a drug volume in the drug delivery device 110. In someembodiments, the processing unit 160 can also include an RFID chipconfigured to store information e.g., the dose remaining information,and allow a near field communication (NEC) device to read the storedinformation. In some embodiments, the processing unit 160 can beconfigured to associate the signal signature with the referencesignature to determine the dose volume remaining in and/or dose injectedby the drug delivery device 110. In some embodiments, the processingunit 160 can also be configured to determine the type of drug deliverydevice 110 coupled to the dose measurement system 100, and/or the drugcontained in the drug delivery device 110. In some embodiments, theprocessing unit 160 can also include a global positioning system (GPS)e.g., to determine a current location of the dose measurement system100.

The communications module 170 can be configured to allow two-waycommunication with an external device e.g., a smart phone app, a localcomputer and/or a remote server. In some embodiments, the communicationsmodule 170 includes a communication interface to provide wiredcommunication with the external device, e.g., a USB or firewireinterface. In some embodiments, the communication interface can also beused to recharge a power source (not shown), e.g., a rechargeablebattery. In some embodiments, the communications module 170 can includemeans for wireless communication with the external device, e.g., Wi-Fi,Bluetooth®, low powered Bluetooth®, Zigbee and the like.

In some embodiments, the communications module 170 can include a displayconfigured to communicate a status of the dose measurement system 100 tothe user e.g., dose remaining, history of use, remaining battery life,wireless connectivity status and/or user reminders. In some embodiments,the status can also include information on whether an injector, forexample, a needle is attached/detached to the drug delivery device 110.Generally a user is required to attach a new injector (e.g., needle) tothe drug delivery device 110 prior to each drug injection. Statusinformation on the injector attachment/detachment can therefore informthe user and/or an external monitor (e.g., a doctor) whether the user isreplacing the injector after each injection.

In some embodiments, the communications module 170 can also includemicrophones and/or vibration mechanisms to convey audio and tactilealerts. In some embodiments, the communications module 170 can include auser input interface, e.g., a button, a switch, an alphanumeric keypad,and/or a touch screen, for example, to allow a user to input informationinto the dose measurement system 100, e.g., power ON the system, powerOFF the system, reset the system, manually input details of a patientbehavior, manually input details of drug delivery device 110 usageand/or manually initiate communication between the dose measurementsystem 100 and a remote device.

The dose measurement system 100 can be disposed in a housing (not shown)that can be configured to be removably coupleable to the drug deliverydevice 110. For example, the lighting module 140, sensing module 150,processing unit 160 and the communications module 170 can beincorporated into a housing, or individual components of the dosemeasurement system 100 (e.g., the lighting module 140 and the sensingmodule 150) can be incorporated into a first housing and othercomponents (e.g., the processing unit 160 and communications module 170)can be separate or incorporated into a second housing. In someembodiments, the housing can be configured (e.g., shaped and sized) tobe removably coupled to at least a portion of the drug delivery device110. For example, the housing can have a recess and/or define a boreinto which a portion of the drug delivery device 110 can be received.The housing can have alignment features to allow the dose measurementsystem 100 to be coupled to the drug delivery device 110 in apredetermined radial orientation. The housing can be opaque and includean insulation structure to prevent interference from ambientelectromagnetic radiation, e.g., to increase signal quality. Forexample, the insulation structure can be a metal lining configured toshield the electronic components of the dose measurement system 100 fromexternal electromagnetic radiation. In some embodiments, the housing cansubstantially resemble a pen cap, e.g., to act as a replacement cap forthe drug delivery device 110 (e.g., an injection pen).

In some embodiments, the lighting module 140 and the sensing module 150can be disposed and oriented in the housing of the dose measurementsystem 100, such that the plurality of light sources are disposed on afirst side, and the plurality of sensors are disposed on a second sideof the drug delivery device 110. In some embodiments, the plurality oflight sources can be disposed at a first radial position with respect tothe drug delivery device 110 and the plurality of sensors can bedisposed at a second radial position which is different than the firstradial position, e.g., the second radial position is approximately 180degrees from the first radial position. In other words, the dosemanagement system 100 can be arranged so that the plurality of lightsources can be disposed on one side of a drug reservoir and theplurality of sensors can be disposed on the opposite side of the drugreservoir. In some embodiments, each of the plurality of light sourcesand the plurality of sensors can be disposed in a substantially straightline. In some embodiments, the plurality of light sources are disposedsuch that each light source is located adjacent to at least one sensor,each light source also located parallel to and in line of sight of atleast one sensor. In some embodiments, at least one of the plurality oflight sources and/or at least one of the plurality of sensors can belocated in an inclined orientation with respect to a longitudinal axisof the drug delivery device 110. In some embodiments, the number of theplurality of sensors can be equal to, greater than or less than thenumber of the plurality of light sources. In some embodiments, theplurality of light sources and the plurality of sensors can beconfigured such that the dose measurement system 110 can detect thevolume of drug in the drug delivery device 110 with a resolution of 1unit of drug or smaller (e.g., fractions of units of drug such as 0.1units, 0.2 units, 0.5 unites, etc.). In some embodiments, the pluralityof light sources and the plurality of sensors can be configured suchthat the dose measurement system 110 can detect the position of aplunger portion of an actuator disposed in the drug delivery device 110with a resolution of 10 micrometers, 20 micrometers, 30 micrometers, 40micrometers, 50 micrometers, 60 micrometers, 70 micrometers, 80micrometers, 90 micrometers, 100 micrometers, 110 micrometers, 120micrometers, 130 micrometers, 140 micrometers, 150 micrometers, 160micrometers, 170 micrometers, 180 micrometers, or 200 micrometers,inclusive of all ranges therebetween.

Having described above various general principles, several exemplaryembodiments of these concepts are now described. These embodiments areonly examples, and many other configurations of a dose measurementsystem, systems and/or methods for measuring dose delivered by a drugdelivery device and overall health of a patient are envisioned.

Referring now to FIGS. 2-4 a dose measurement system 200 can include alighting module 240, a sensing module 250, a processing unit 260, acommunications module 270 and a power source 286. The dose measurementsystem 200 can be configured to be removably coupleable to a drugdelivery device 210 (also referred to herein as “an injection pen 210”).The drug delivery device 210 can be configured to deliver a predefinedquantity of a drug (e.g., dose) to a patient. Examples of the drugdelivery device 210 include insulin injection pens that can be used by apatient to self administer insulin. As described herein, the drugdelivery device 210 can include a housing 212, an actuator 214 and aninjector 216. The housing 212 can be relatively opaque, such that itonly allows select wavelengths of electromagnetic radiation to betransmitted therethrough, e.g., infrared or microwave radiation. Thehousing 210 defines an internal volume (e.g., reservoir) for storing adrug. The actuator 214 can include a plunger portion in fluidcommunication with the drug and configured to communicate a predefinedquantity of drug to the patient. The actuator 214 can be configurable,e.g., by the user, to dispense variable quantities of the drug. Theinjector 216 is configured to penetrate a user's skin for intramuscular,subcutaneous, and/or intravenous delivery of the drug.

The dose measurement system 200 includes a housing 220 that includes atop housing portion 222 (also referred to herein as “top housing 222”)and a bottom housing portion 224 (also referred to herein as “bottomhousing 224”). The top housing portion 222 and the bottom housingportion 224 can be removably or fixedly coupled together by, e.g.,gluing, hot welding, a snap-fit mechanism, screwed together, or by anyother suitable coupling means. The housing 220 can be made from a rigid,light weight, and opaque material, e.g., polytetrafluoroethylene, highdensity polyethylene, polycarbonate, other plastics, acrylic, sheetmetal, any other suitable material or a combination thereof. The housing220 can also be configured to shield the internal electronic componentsof the dose measurement system 200 from environmental electromagneticnoise. For example, the housing can include an insulation structure (notshown) such as, for example, lined with aluminum or any other metalsheet or foil that can serve as an electromagnetic shield.

As shown in FIG. 3, the top housing portion 222 defines an internalvolume for substantially housing the lighting module 240, the sensingmodule 250, the processing unit 260, the communications module 270 andthe power source 286. The bottom housing portion 224 defines a bore 226,shaped and sized to receive at least a portion of the drug deliverydevice 210. For example, the bore 226 can be shaped and sized to receiveonly the drug containing portion of the housing 212 and the injector216. The bore 226 can be configured to receive the drug delivery device210 in a preferred orientation, e.g., a preferred radial orientation. Insome embodiments, the bore 226 can be in close tolerance with thediameter of the drug delivery device 210, e.g., to form a friction fitwith the drug delivery device 210. In some embodiments, the bore 226 caninclude notches, grooves, detents, any other snap-fit mechanism, orthreads, for removably coupling the drug delivery device 210 to thebottom housing 224. In some embodiments, bottom housing portion 224 caninclude alignment features to allow the drug delivery device 210 to becoupleable with the dose measurement system 200 in a predeterminedradial orientation.

In some embodiments, the bottom housing 224 can include apertures 228for receiving at least a portion of the plurality of light sources 244of the lighting module 240, and/or sensors 254 of the sensing module250. The apertures 228 can be configured to provide mechanical supportfor the light sources 244 and/or sensors 254, or can serve as analignment mechanism for the lighting module 240 and/or sensing module250.

As shown in FIG. 4, the top housing 222 includes an opening 230 forreceiving at least a portion of the communications module 270 such as,for example, a communication interface to provide wired communicationwith an external device, and/or an interface for charging the powersource 286. In some embodiments, the top housing 222 can also includefeatures, e.g., recesses, apertures, cavities, etc. for receiving aportion of the drug delivery device 210 such as, e.g., the injector 216.In some embodiments, the housing 220 can also include a detectionmechanism (not shown) to detect if the drug delivery device 210 has beencoupled to the dose measurement system 200, e.g., a push switch, amotion sensor, a position sensor, an optical sensor, a piezoelectricsensor, an impedance sensor, or any other suitable sensor. The housing220 can be relatively smooth and free of sharp edges. In someembodiments, the housing 220 can be shaped to resemble a pen cap thathas a form factor that occupies minimal space, e.g., can fit in thepocket of a user. In some embodiments, the housing 220 can also includefeatures, e.g., clips for attaching to a user's shirt pocket, and/orother ornamental features. In some embodiment, the dose measurementsystem 200 can also serve as a replacement cap for the drug deliverydevice 210. In some embodiments, the housing 220 can also includesensors (e.g., optical sensors) determine a status of the drug deliverydevice 210, for example, if the injector 216 (e.g., a needle) isattached/detached to the drug delivery device 210.

Referring still to FIGS. 3 and 4, the plurality of light sources 244(e.g., LEDs) of the lighting module 240 are mounted on, or otherwisedisposed on, a printed circuit board (PCB) 242. The PCB 242 can be anystandard PCB made by any commonly known process. In some embodiments,the plurality of light sources 244 can be arranged in a straight lineand equally spaced such that, when the portion of the drug deliverydevice 210 that defines the internal volume of the housing 212 holdingthe drug is coupled with the dose measurement system 200, the lightsources 244 can illuminate the entire internal volume. In someembodiments, the light sources 244 can be placed in any otherconfiguration, e.g., a zig zag pattern, unequally spaced, staggeredorientation, alternately disposed with the sensors 254, or any otherconfiguration as described herein.

In some embodiments, the light sources 244 can be configured to producean electromagnetic radiation of a wavelength that is capable ofpenetrating through the housing 212 of the drug delivery device 210, thedrug contained therein, and/or a portion of the housing 220. Forexample, infrared radiation or microwave radiation can penetrate many ofthe plastic materials that are commonly used in manufacturing drugdelivery devices (e.g., injection pens). In some embodiments, anelectromagnetic radiation has a frequency that can also penetratethrough the internal components of the drug delivery device 210, e.g.,the plunger portion of the actuator 214. In some embodiments, the lightsources 244 can be configured to produce a wide beam of electromagneticradiation, e.g., wide angled LEDs. Said another way, the electromagneticradiation cone of a single light source 244 can have a wide angle andthe electromagnetic radiation cones of adjacent light sources 244 canoverlap. In some embodiments, the plurality of light sources 244 can beconfigured to emit pulses of electromagnetic radiation, e.g., a seriesof less than 100 microsecond pulses.

The plurality of sensors 254 of the sensing module 250 are mounted on,or otherwise disposed on, a PCB 252. The PCB 252 can be any standard PCBmade by any commonly known process. The plurality of sensors 254 can beany optical sensors (e.g., photodiodes) optically coupleable with theplurality of light sources 244 and configured to detect at least aportion of the electromagnetic radiation emitted by the plurality oflight sources 244. The electromagnetic radiation can be transmittedradiation, refracted radiation (e.g., refracted through air, drug,and/or body of drug delivery device 210), reflected radiation (e.g.,reflected from a wall of the housing 220 or internally reflected from awall of the drug delivery device 210), or multi-directionalrefraction/reflection caused by a lensing effect of a curved surface ofthe housing 212 and/or the drug reservoir. The transmitted, refracted,and reflected electromagnetic signal received by the plurality ofsensors 254 can be used to create a signal signature (e.g., by theprocessing unit 260). For example, the signal signature can then beassociated with a reference signature to determine the dose remaining inthe drug delivery device 210. In some embodiments, the signal responseof the sensors 254 can be used to measure usability metrics such as, forexample, determining the presence of the injector 216 of the drugdelivery device 210, and/or determining whether the drug delivery device210 is coupled/uncoupled to the dose measurement system 200. In someembodiments, the signal response of the sensors 254 can also be used todetermine the type of a drug delivery device 210 is coupled to the dosemeasurement system 200, and/or the type of drug present in the drugdelivery device 210.

In some embodiments, the sensors 254 can be arranged in a substantiallysimilar configuration to the light sources 244. In some embodiments, thenumber of sensors 254 can be greater or less than the number of lightsources 244. In some embodiments, the light sources 244 and sensors 254can be arranged such that each PCB 244, 254 includes a combination oflight sources 244 and sensor 254, e.g., arranged alternatively. In someembodiments, the light sources 244 and/or sensors 254 can be arranged inan inclined orientation.

The processing unit 260 can include a PCB 262 and a processor 264. ThePCB 262 can be any standard PCB made by any commonly known process andcan include amplifiers, transistors and/or any other electroniccircuitry as necessary. The processor 264 can be any processor, e.g., amicroprocessor, a microcontroller, a PLC, an ASIC chip, an ARM chip, anADC, or any other suitable processor. The processing unit 260 can becoupled to the lighting module 240 and the sensing module 250 usingelectronic couplings 266, such that the lighting module 240 and thesensing module 250 are oriented perpendicular to the processing unit 260and parallel to each other. In some embodiments, the processing unit 260can include an onboard memory for at least temporarily storing a signalsignature, a reference signature database, dose information, user healthdata (e.g., blood glucose level), device location data (e.g., from a GPSoptionally included in the dose measurement system 200 or from anotherGPS enabled device that is paired with the system 200 such as a bloodglucose meter or cellular phone), and any other data as might be usefulfor a patient to manage their health. In some embodiments, theprocessing unit 260 can include an RFID chip configured to storeinformation and allow an NFC device to read the information storedtherein. The processing unit 260 can be configurable to control theoperation of the dose measurement system 200, for example, activationand timing of the light sources 244, and/or reading and processing ofelectromagnetic radiation data from the sensors 254. For example, theprocessing unit 260 can be configured to compare electromagneticradiation signal signature obtained form the plurality of sensors 254and associate it with the reference signature database to determine thequantity of dose remaining in the drug delivery device 210 or theposition of the actuator 214 (e.g., plunger) of the drug delivery device210.

In some embodiments, the processing unit 260 can be configured tocorrect the signal signature for background noise. For example, theprocessing unit 260 can be configured to operate the sensing module 250to detect a background signature with the lighting module in dark state,i.e., each of the plurality of light sources 244 switched off. Thebackground signature can then be associated with the signal signature tocorrect for background noise. In some embodiments, the processing unit260 can also include electronic signal filtering algorithms, e.g.,Fourier transforms, low pass filter, band filter, high pass filter,Bessel filter, or any other digital filter to reduce noise and increasesignal quality. The processing unit can also be configured to obtainreference signatures by storing the electromagnetic radiation signaldetected by the sensing module 250 for a range of dose volumes in arepresentative drug delivery device 210, e.g., electromagnetic radiationsignal at drug delivery device 210 full, empty and a series of intervalstherebetween, e.g., every unit of dose dispensed from the drug deliverydevice and/or every 170 micrometer displacement of a plunger portion ofthe actuator 214 included in the drug delivery device 210.

In some embodiments, the processing unit 260 can be configured toinclude probabilistic matching algorithms that can be used to associatethe signal signature with the reference signature to determine a volumeof liquid in the drug delivery device 210. In some embodiments, theprocessing unit 260 can also include algorithms to determine the type ofdrug delivery device 210 coupled to the dose measurement system 200and/or the drug contained within the drug delivery device 210, from thesignal signature. For example, drug delivery devices 210 of the sameform factor (i.e., size and shape) can include different drugs, forexample, insulin, epinephrine, or any other drug. In order to avoidconfusion, delivery device 210 manufactures often provide marking,labeling, or color coding to distinguish between different drugs indelivery devices 210 that look similar. Said another way, once a drugdelivery device 210 company has designed and is manufacturing aparticular delivery device 210, they often use that same design fordifferent drug therapies. Therefore, in some embodiments, the algorithmsincluded in the processing unit 260 can be configured to determine thetype of drug delivery device 210 coupled to the dose measurement system200 based on, for example, material properties (e.g., color, refractiveindex, etc.) of the device. For example, different materials and/orcolors can have different refractive indexes, which can be used foridentification. In some embodiments, the type of drug included in thedrug delivery device 210 can also be used to determine the type ofdelivery device 210 based on the refractive index of the drug.

The processing unit 260 can also be configured to control and operatethe communications module 270. In some embodiments, the processing unit260 can be configured to operate the system in a power efficient manner.For example, the processing unit 260 can turn of the electronicspowering the light sources 244, e.g., operational amplifiers when theyare not needed. The processing unit 260 can pulse the LEDs for a shortperiod at high current e.g., to save power and increase signal to noiseratio. The processing unit 260 can also be configured to periodicallyactivate the communications module 270, e.g., 10 times per day or whenthe dose measurement system 200 is attached to the drug delivery device210, and/or turn it off when it is not needed. In some embodiments, theprocessing unit 260 can also include a global positioning system (GPS)e.g., to determine a current location of the dose measurement system200.

The communications module 270 can be configured to communicate data tothe user and/or an external device, for example, a smart phoneapplication, a local computer, and/or a remote server. The communicateddata can include, e.g., initial system activation, system ON/OFF, drugdelivery device 210 coupled/uncoupled, injector attached/detached fromdrug delivery device 210, dose remaining, dose history, time, system ordrug temperature, system location (GPS), drug delivery device 210coupling/uncoupling data, drug expiration date, velocity at which drugis delivered, device collisions, device power remaining, step count,tampering with the system, any other user health information and/or anyother usable data. In some embodiments, the communications module 270can also be configured to receive data, for example, new calibrationdata, firmware updates, user health information (e.g., blood glucoselevels, diet, exercise, dose information) and/or any other informationinput by the user, or communicated by an external device. Thecommunications module 270 can include conventional electronics for datacommunication and can use a standard communication protocol, e.g.,Wi-Fi, Bluetooth®, low powered Blue-tooth®, Zigbee, USB, firewire,and/or near field communication, e.g., infrared. In some embodiments,the communications module 270 can be configured to periodically connect,e.g., 10 times per day, to the external device, e.g., a smart phone, tolog any dose data stored in the onboard memory. In some embodiments, thecommunications module 270 can be activated on demand by the user.

Referring now also to FIG. 5, in some embodiments, the communicationsmodule 270 can include a communication interface 271 located on anexternal surface of the housing 210 of the dose measurement system 200for communicating with the user. The communication interface 271 caninclude a switch 272, e.g., a power switch, a reset button, and/or acommunication switch to manually initiate communication with an externaldevice, e.g., activate Bluetooth®. In some embodiments, thecommunications interface 271 can also include an indicator 274 such asalight source (e.g., an LED) to indicate to the user, for example, ifthe dose measurement system 200 is ON/OFF, or the communication module270 is active. In some embodiments, the communication interface 271 caninclude a display 276 for visual communication of information to theuser, e.g., the dose remaining 278 in the drug delivery device 210, thecurrent time 280, system power remaining 282, dose history 284 such as,e.g., average dose usage, time last dose taken, etc, and/or wirelessconnectivity status. In some embodiments, the communications interface271 can include an alphanumeric keypad, and/or a touch screen, forexample, to allow a user to input information (e.g., food intake,exercise data, etc.) into the dose measurement system 200. In someembodiments, the communications module 270 can include a microphone forproviding audible alerts or messages to the user, e.g., dose reminders,reinforcement messages, and/or a microphone for receiving audio inputfrom the user. In some embodiments, the communications module 270 caninclude means for tactile alerts, e.g., a vibration mechanism. In someembodiments, the communications module 270 can communicate otherinformation pertaining to user health, e.g., steps taken, caloriesburned, blood glucose levels, and/or any other information.

The power source 286 can be any power source that can be used to powerthe dose measurement system 200. In some embodiments, the power source286 can include a disposable battery. In some embodiments, the powersource 286 can include a rechargeable battery, e.g., a NiCad battery, aLi-ion battery, Li-polymer battery, or any other battery that has asmall form factor, (e.g., of the type used in cell phones), and/or doesnot to be charged frequently, e.g., charged once per month. In someembodiments, the power source 286 can be charged using an external powersource, e.g., though a power socket located on the housing 220 orthrough a communication interface of the communications module 270,e.g., a USB interface. In some embodiments, the power source 286 can becharged using solar energy and can include solar panels. In someembodiments, the power source 286 can be charged using kinetic energyand can include mechanical energy transducers.

As described above, the plurality of sensors 254 of the sensing module250 are configured to receive at least one of a transmitted radiation,refracted radiation, e.g., refracted through air, the liquid drug, thehousing 212 of drug delivery device 210, reflected radiation, e.g.,reflected from a wall of the housing 220 or internally reflected from awall of the internal volume of the drug delivery device 210, ormulti-directional reflection/refraction caused by a lensing effect of acurved surface of the housing 212 of the drug delivery device 210.Referring now to FIG. 6, a light source L (e.g., a wide angle lightsource) can produce a plurality of light rays emanating and divergingaway from the light source. The light source L is present in a firstmedium M1 (e.g., air) having a first refractive index n1. A secondmedium M2 (e.g., liquid drug) having a second refractive index n2,greater than the first refractive index (i.e., n2>n1), is bordered bythe first medium M1 on both sides. The second medium M2 can also includean opaque surface, e.g., a sidewall.

A first light ray L1 emitted by the light source L is incident on theinterface of the first medium M1 and the second medium M2 at a firstangle of 0 degrees. This light ray does not bend as it penetratesthrough the second medium M2 and transmits back into the first medium M1(the transmitted light) at the original angle of incidence. A secondlight ray L2 is incident on the interface of the first medium M1 and thesecond medium M2 at a second angle >0. The second light ray L2 bends orrefracts (the refracted light) as it penetrates the second medium M2,and then bends again to its original angle of incidence as it reentersthe first medium M1, parallel to but offset from the emitted ray L2. Athird light ray L3 is incident on the interface of the first medium M1and the second medium M2 at a third angle greater than the second angle.At this angle of incidence, the light ray L3 does not penetrate into thesecond medium M2, but it is reflected back into the first medium M1 (thereflected light), such that angle of reflection is equal to the angle ofincidence. A fourth light ray L4 is incident on the interface of thefirst medium M1 and the second medium M2 at a fourth angle less then thethird angle, such that the light ray L4 refracts in the second mediumM2, but is now incident on the opaque surface included in the secondmedium M2 (reflection from opaque surface). At least a portion of thelight ray L4 is reflected back into the second medium M2, which thenreenters back into the first medium M1 at a fifth angle, such that thefifth angle is not equal to the fourth angle.

As described herein, the electromagnetic radiation signal received bythe plurality of sensors 254 of the sensing module 250 can include acombination of the transmitted, refracted and reflected portions of theelectromagnetic radiation. A unique signal signature is produced by thecombination of the portions of the electromagnetic radiation atdifferent dose volumes remaining, and/or the actuator 216 position ofthe drug delivery device 210. This signal signature can be compared witha reference signal signature database (also referred to herein as “acalibration curve”) to obtain the volume of dose remaining in drugdelivery device 210, as described in further detail herein.

Referring now to FIGS. 7-10, various configurations of the light sourcesand the sensors are shown and described. While the transmitted andreflected portion of the electromagnetic radiation emitted by the lightsources is shown, the refractive portion is not shown for clarity. Asshown in FIG. 7, a dose measurement system 300 includes a plurality oflight sources 344 and a plurality of sensors 354. A drug delivery device310 is coupled to the dose measurement system 300. The drug deliverydevice 310 includes a housing 312 and an actuator 314 that collectivelydefine an internal volume (e.g., reservoir) for containing a drug. Thedrug delivery device 310 also includes an injector 316 for communicatingthe drug to a patient. The dose measurement system 300 is configuredsuch that the plurality of light sources 344 are disposed on a firstside of the housing oriented towards the drug delivery device 310 andthe plurality of sensors 354 are disposed on a second side of thehousing such that each of the plurality of sensors 354 is substantiallyopposite to, and in optical communication with, at least one of theplurality of light sources 344. In some embodiments, the plurality oflight sources 344 and/or the plurality of sensors 354 can be disposed ina substantially linear relationship (e.g., a straight line) with respectto each other. Each of the plurality of sensors 354 receive acombination of transmitted, refracted and reflected electromagneticradiation emitted by the of tight sources 344. The reflection portion ofthe electromagnetic radiation can be reflected from a plunger portion ofthe actuator 314, and/or reflected from a housing of the dosemeasurement system 300 or the housing 312 of the drug delivery device310. The refraction can be from the housing 312 and/or from the liquiddrug disposed in the drug delivery device 310. The combination of thetransmitted, reflected and refracted portions of the electromagneticradiation detected by each of the plurality of sensors yields a uniquesignal signature for a range of dose volumes remaining in the drugdelivery device 310.

In some embodiments, a plurality of light sources and a plurality ofsensors can be alternately disposed both sides of a drug deliverydevice. As shown in FIG. 8, a dose measurement system 400 includes aplurality of light sources 444 and a plurality of sensors 454. The drugdelivery device 410 includes a housing 412 and an actuator 414 thatcollectively define an internal volume (e.g., reservoir) for containinga drug. The drug delivery device 410 also includes an injector 416 forcommunicating the drug to a patient. The dose measurement system 400 isconfigured such that the plurality of light sources 444 and theplurality of sensors 454 are disposed on both sides of the drug deliverydevice. In other words, each side of the drug delivery device 410 has aplurality of light sources 444 and a plurality of sensors 454. This canbe advantageous as emission and detection of electromagnetic radiationis now performed from both sides of the drug delivery device 410, whichcan, for example, remove any biases.

In some embodiments, at least a portion of the plurality of lightsources and/or the plurality of sensors can be arranged in an angularorientation. As shown in FIG. 9, a dose measurement system 500 includesa plurality of light sources 544 and a plurality of sensors 554. Thedrug delivery device 510 includes a housing 512 and an actuator 514 thatcollectively define an internal volume (e.g., reservoir) for containinga drug. The drug delivery device 510 also includes an injector 516 forcommunicating the drug to a patient. The dose measurement system 500 isconfigured such that the plurality of light sources 544 and theplurality of sensors 554 are disposed on both side of the drug deliverydevice 510 and have an angular orientation with respect to alongitudinal axis of the dose measurement system 500 and drug deliverydevice 510. This orientation can ensure that the electromagneticradiation emitted by the plurality of light sources 544 is incident on alarger portion of the drug delivery device 510 then can be achievablewith a the light sources 544 oriented in a straight line. Similarly, theplurality of sensors 554 can also detect a greater portion of theelectromagnetic radiation. This can, for example, result in higherresolution of the sensors 554, and/or reduce the quantity of lightsources 544 and/or sensors 554 required to achieve the desiredresolution.

In some embodiments, wider angle LEDs, for example, can also be usedensure that the electromagnetic radiation emitted by the plurality oflight sources 544 is incident on a larger portion of the drug deliverydevice 510 than can be achievable with a narrower beam light sources544. In other words, with a wider beam emitted by the light sources 544,a higher proportion of the overall drug delivery device 510 (or of thedrug reservoir) is in optical communication with the light sources 544.Since a higher proportion of the delivery device 510 is in opticalcommunication with the light sources 544, a broader spectrum ofelectromagnetic radiation being transmitted, reflected and/or refractedthrough the drug delivery device can increase the signal strengthdetectable by the plurality of sensors 554. Said other way, variabilityin the signal signatures (as opposed to increased intensity of lightincident on the sensor) increases with the broadening of the beam oflight incident on the delivery device, therefore increasing theresolution of the dose measurement system 500. For example, wider anglesmay increase ability to distinguish states of the drug delivery device,even though the overall intensity of light may be lower. This is becausedistinguishing states is more about optimizing how the intensity oflight changes from state to state than it is about the absoluteintensity of light.

In some embodiments, a dose measurement system can be configured todetect a signal signature from a location of an actuator of a drugdelivery device, which can be used to estimate the dose remaining in thedrug delivery device. As shown in FIG. 10, a dose measurement system 600includes a plurality of light sources 644 and a plurality of sensors654. A drug delivery device 610 is coupled to the dose measurementsystem 600. The drug delivery device 610 includes a housing 612 and anactuator 614 that collectively define an interior volume (e.g.reservoir) for containing a drug. The dose measurement system 600 isdisposed generally about the actuator 614 portion of the drug deliverydevice 610 as opposed to the dose measurement systems 300, 400 and 500being disposed generally around the drug reservoir as shown in FIGS.7-9. The plurality of light sources 644 and sensors 654 are configuredand arranged in a substantially similar way as described above withreference to FIG. 7. Electromagnetic radiation emitted by the pluralityof light sources 644 can be transmitted unblocked by the actuator 614,blocked by a plunger portion of the actuator 614, reflected by a body orthe plunger portion of the actuator 614 and/or reflected/refracted bythe housing the drug delivery device 610. The combination of thetransmitted, reflected and refracted portions of the electromagneticradiation detected by the plurality of sensors 654 are then used togenerate a signal signature at a given position of the actuator 614.Displacement of the actuator 614 from a first position to a secondposition changes the transmission, reflection and refraction pattern ofthe electromagnetic radiation detected by the sensors 654, creating aunique signal signature at each position of the actuator 614. Thissignature can be correlated to the dose volume remaining in the drugdelivery device 610, e.g., by association with a reference signature.

Referring now to FIGS. 11A-11C, each sensors of the plurality of sensorsof a dose measurement system can detect the electromagnetic radiationemitted by at least a portion of the plurality of light sources, and thedetected electromagnetic radiation can be a combination of transmittedreflected and refracted electromagnetic radiation. As shown, the dosemeasurement system 700 includes two light sources 744 a and 744 b, andtwo sensors 754 a and 754 b for clarity. The dose measurement system 700is coupled to a drug delivery device 710 which includes a housing 712and an actuator 714 that collectively define an internal volume (e.g.,reservoir) for containing a liquid drug. The drug reservoir and at leasta plunger portion of the actuator 714 are disposed substantially insidethe dose measurement system 700 between the light sources 744 a, 744 band sensors 754 a, 754 b.

As shown in FIG. 11A, the plunger portion of the actuator 714 is in afirst position (position 1) such that the plunger portion is not in theline of sight of light sources 744 a and 744 b and sensors 754 a and 754b. When electromagnetic radiation is emitted by the light sources 744 aand 744 b towards the drug delivery device 710, a significant portion ofthe electromagnetic radiation is detected by the sensors 754 a and 754 bin position 1. The electromagnetic radiation can include transmittedradiation, reflected radiation (e.g., by the housing 712 of the drugdelivery device 710) and refraction, (e.g., by the liquid drug and/orhousing), and multi-direction reflection/refraction because of a curvedsurface of the housing 712 of the drug delivery device 710 as describedin more detail below. As shown in this example, sensor 754 a value is15.3 and sensor 754 b value is 13.7, which indicates that a significantportion of the electromagnetic radiation is detected by the sensors 754a and 754 b.

As shown in FIG. 11B, the actuator is 714 has been displaced to a secondposition (position 2) such that the plunger portion partially blocks theline of sight between the light source 744 b and the sensor 754 b. Inposition 2, a significant portion of the electromagnetic radiationemitted by the light source 744 b is blocked from reaching the sensor754 b by the actuator 714, but at least a portion of the electromagneticradiation emitted by light source 744 a can still reach the sensor 754 balong with any multi-directional reflected/refracted electromagneticradiation. Furthermore, Sensor 754 a can receive refractedelectromagnetic radiation from sensor 744 b and transmitted, refractedradiation from Sensor 744 a. It also receives electromagnetic radiationreflected by a surface of the plunger that at least partially definesthe drug reservoir. Therefore, at position 2 the sensor 754 a detects anelectromagnetic radiation value of 15.5 (greater than position 1), andsensor 754 b detects an electromagnetic radiation value of 8.8 (lessthan position 1). The unique values measured at position 2 can serve asthe signal signature values for position 2.

As shown in FIG. 11C, the plunger portion of the actuator 714 is in athird position (position 3) such that the plunger portion of theactuator 714 completely blocks the line of sight of the sensor 754 afrom the electromagnetic radiation emitted by light source 744 a, suchthat substantially no transmitted and or reflected radiation from lightsource 744 a can reach the sensor 754 a. A portion of the transmittedelectromagnetic radiation emitted by the light source 744 b is alsoblocked by at least a portion of the actuator 714, from reaching thesensor 754 b. Both the sensors 754 a and 754 b can still receive atleast a portion of the reflected and refracted portions of theelectromagnetic radiation emitted by any of the light sources 744 aand/or 744 b. Therefore, at position 3 the sensor 754 a detects anelectromagnetic radiation value of 2.2 (less than positions 1 and 2),and sensor 754 b detects an electromagnetic radiation value of 12.0(less than position 1, but greater than position 2). The unique valuesmeasured at position 3 can serve as the signal signature values forposition 3.

Referring now to FIG. 12, a cross section of the dose measurement system700 taken along line AA in FIG. 11A is shown to illustrate the lensingeffect caused by the curvature of the drug reservoir. As shown, a lightray emitted at a zero degree angle by light source 744 b is transmittedwithout bending towards the sensor 754 b. Two more light rays emitted bythe light source 744 b, at an angle away from the transmitted ray, arecaused to refract (bend) towards the transmitted ray as they enter thedrug reservoir because the liquid drug has a higher refractive indexthan air. This phenomenon is referred to herein as “a lensing effect,”which can result in focusing of the light rays towards the sensor 754 b.A fourth ray is emitted at an angle further away from the transmittedray such that it refracts at the air/drug interface, and then is furtherreflected by an internal surface of the housing 712 of the drug deliverysystem 710 such that it is incident on the sensor 754 b. A fifth ray isemitted at an angle, such that even after refrac not incident on thesensor 754 b. As described above, the combination of these rays yields adetected electromagnetic radiation value of 15.3 by sensor 754 a and13.7 by sensor 754 b. These unique values measured at position 1 canserve as the signal signature values for position 1.

Referring now to FIG. 13, a cross section of the dose measurement system700 taken along line BB in FIG. 11C is shown to illustrate effect of theactuator 714 on the transmission of light. As shown, a light ray emittedat a zero degree angle by light source 744 b is blocked by a portion ofthe actuator 714. Two more light rays emitted by the light source 744 b,at an angle away from the transmitted ray, pass unretracted (refractionthrough the housing is ignored) through the portion of the housing 712of the drug delivery device 710 (there is no drug in this portion of thedevice 710) and are incident on the sensor 754 b. A fourth ray isemitted by the light source 744 b at an angle, such that it isinternally reflected by the housing 712 and is incident on sensor 754 b,while a fifth ray is internally reflected by the housing 712 but is notincident on the sensor 754 b. The combination of these rays yields adetected electromagnetic radiation value of 2.2 by sensor 754 a and 12.0by sensor 754 b. These unique values measured at position 3 can serve asthe signal signature values for position 3. It is to be noted thatalthough the line of sight of sensor 754 a is completely blocked fromlight source 744 a, reflected and refracted portions of theelectromagnetic radiation still contribute to generation of a positivevalue.

Although the sensor values for particular positions are described asbeing absolute values, individual sensor values relative to other sensorvalues can be used to infer and/or determine the volume of liquidremaining in the drug reservoir. For example, sensor 754 a having aparticular value that is different from sensor 754 b value by a certainamount or a certain percentage can be indicative of a position/drugvolume remaining. Furthermore, a sensor value relative to two or moreother sensor values can be used to generate a calibration curve of adrug delivery device 710.

A unique signal signature obtained at various configurations pertainingto the volume of dose dispensed by a drug delivery device can be used toobtain a reference signature (calibration curve) of the dose measurementsystem. FIG. 14 shows an example of a reference signal signatureobtained for a drug delivery device using a dose measurement system thatincludes a total of seven sensors. The dose measurement system can beany dose measurement system as described herein. The electromagneticradiation signature detected by each of the plurality of sensors for arange of dose volumes dispensed is stored and used to create thereference signature. As can be seen from the reference signature whenthe drug delivery device is almost full, sensor 1 records low amplitudeof electromagnetic radiation, while sensor 7 records very high amplitudeof electrode and all other sensors detect some intermediate signalsignature. In contrast, when the drug delivery is completely empty,sensor 1 records very high amplitude of electromagnetic radiation, whilesensor 7 records low amplitude and all other sensors detect someintermediate signal signature.

Sensor 8 detects a uniform sensor signal for a substantial portion ofthe dose delivered, until the almost all the dose has been delivered orthe drug delivery device is almost empty. In some embodiments, thesensor 8 can also be used as the volume critically low sensor, e.g., toindicate that the drug delivery device is completely empty. In someembodiments, the sensor 8 can also be used as a usability metric sensor,e.g., to detect if a drug delivery device is coupled to the dosemeasurement system and/or an injector included in the drug deliverydevice is present or not.

Therefore in this manner, the signal value recorded from all sensors fora range of drug volumes remaining yields the signal signature for theentire volume of drug in the drug delivery device. The range of drugvolumes used for obtaining the signal signature can include e.g., drugdelivery device completely full, drug delivery device completely empty,and a sufficient number of intermediate signatures e.g., a signatureobtained every unit of the total fluid dispensed, inclusive of allpercentages therebetween.

In some embodiments, the reference signature can be corrected forbackground light. For example a background signature can be detected bydetecting the signal signature from the plurality of sensors in a darkstate of the plurality of light sources. The signal signature can becompared with the background signature to remove background noise. Insome embodiments, the signal signature is associated with the referencesignature to determine a drug volume in the drug delivery device, usingprobabilistic matching algorithms. In some embodiments, the plurality oflight sources and the plurality of sensors can be configured such thatthe dose measurement system can detect the volume of drug in the drugdelivery device with a resolution of 1 unit of drug, and/or position ofa plunger portion of an actuator disposed in the drug delivery device110 with a resolution of 100 micrometers, 110 micrometers, 120micrometers, 130 micrometers, 140 micrometers, 150 micrometers, 160micrometers, 170 micrometers, 180 micrometers, or 200 micrometers,inclusive of all ranges therebetween.

FIG. 15 illustrates a flow diagram showing a method 800 for measuringdose remaining in a drug delivery device using any of the dosemeasurement systems described herein. A user attaches a dose measurementsystem to a drug delivery device 802. A plurality of sensors disposed inthe dose measurement system scan the drug delivery device to determinethe dose remaining 804. For example, a processing unit of the dosemeasurement system can associate the signal signature detected by theplurality of sensors with a reference signature to determine the doseremaining. The sensor data is recorded on an onboard memory 806, e.g.,an RFID chip and/or a memory that is part of the processing unit of thedose measurement system. The dose measurement system alerts the user ifthe dose remaining is critically low 808. Any one of audio, visual ortactile alerts can be used to alert the user. A communications module ofthe dose measurement system searches for an external device 810. Forexample, a Bluetooth® connection can be activated to search for theexternal device, e.g., a smart phone app, a local computer or a remoteserver. The dose measurement system pairs with the external device andlogs dose remaining data on the external device and/or receives anyfirmware updates 812. Optionally, the dose measurement system can alsoalert a user when it is time to take a dose 814. After dose data hasbeen recorded and transmitted to an external device, the user can removethe dose measurement system from the drug delivery device 816. The userthen injects a pre determined volume of the dose using the drug deliverydevice 818. The user finally replaces the dose measurement system on thedrug delivery device 820. The method 800 can then be repeated.

FIG. 16 illustrates a flow diagram showing a method 900 for conservingpower when the dose measurement system is not in use. The method 900described herein can be used with any of the dose measurement systemsdescribed herein. In a first step, a detection mechanism of the dosemeasurement system checks for a drug delivery device 902. The drugdelivery device can either be coupled or uncoupled to the dosemeasurement system 904. If the drug delivery device is not attached, thedose measurement system automatically checks for outstanding data in thememory to be logged to an external device or the user can activate acommunications module of the dose measurement system 906. In someembodiments, the communications module is only activated when the dosemeasurement system is attached to a drug delivery device. The dosemeasurement system then determines if there is onboard data to be loggedand if an external device was found 908. If there is no onboard data tobe logged and no external device was found, the dose measurement systemgoes into a power save mode for a predefined time “X” 910. For example,a processing unit of the system can turn off a communications module ofthe dose measurement system and/or turn off the electronics controllinga plurality of light sources and/or plurality of sensors of the dosemeasurement system. Time “X” can be, e.g., 1 minute, 10 minutes, 1 hour,or any time therebetween. Alternatively, if there is data to be loggedand an external device was found, the dose measurement system pairs withthe external device and logs data on the external device and/or receivesany firmware updates from the external device 912. The dose measurementsystem can then go into the power save mode 910. If instead a drugdelivery device was found to be attached to the dose measurement system904, the dose measurement system scans the drug delivery device andcollects signal from all of the plurality of sensors 914. The signalfrom each of the plurality of sensors can be used to create a signalsignature corresponding to the dose remaining in the drug deliverydevice. A processing unit of the dose measurement system compares thesignal signature with a reference signature to estimate dose remainingin the drug delivery device 916. The dose measurement system determinesif the dose injected was greater than zero 918. If the dose injected wasgreater than zero, the dose measurement system time stamps and storesthe dose on an onboard memory 920. The dose measurement system then goesinto the power save mode for the time “X” 910. If the dose injected wasnot greater than zero 918, than the dose measurement system directlygoes into the power save mode for the time “X” 910.

In some embodiments, any of the dose measurement systems describedherein can be associated with a health management system to manage thehealth of a patient suffering from Type I or II diabetes. FIG. 17 showsa schematic block diagram of a health management system 1000 formanaging the health of a diabetic user U. In some embodiments, thehealth management system can be a smart phone application. In someembodiments, the health management system can be a local computer or aremote server. The health management system is in two way communicationwith a dose measurement system 1100 that can be reversibly coupled to adrug delivery device 1110. The drug delivery device 1110 can be aninsulin injection pen or syringe for administering insulin to a user U.The dose measurement system can also communicate information to a useror receive an input from the user. The health management system 1000 isconfigured to receive the user exercise data E and diet data D. Thehealth management system 1000 is also configured to receive bloodglucose data from a blood glucose sensor 1200. The health managementsystem 1000 can further be configured to receive user health data from ahome health monitor 1300, e.g., weight, blood pressure, EKG, oxygensaturation, actigraphy measures, pulmonary function, water retention,temperature, etc. The health management system 1000 can be in two waycommunication with a network 1400. The network can be, for example, aremote server or a call center. The network 1400 can also be in two waycommunication with a monitor M and an authorized drug dispenser DD. Themonitor M can be a doctor, a care giver, a pharmacy, and/or a clinicaltrial manager. The authorized drug dispenser DD can be a pharmacy or aclinical trial manager.

In some embodiments, the dose measurement system 1100 communicates tothe health management system the insulin dose remaining in and/or theinsulin dose delivered to the user U by the drug delivery device 1110.In some embodiments, the health management system can also include amemory for storing the user U insulin dose regimen and/or any othermedication schedule. The user U medication regimen can be communicatedto the health management system 1100 by, for example, the monitor Mand/or the authorized drug dispenser DD through the network 1400. Insome embodiments, the health management system 1100 can also be used toprocess user U health data, for example, user U blood glucose levels,exercise data E, diet data D, and/or home health monitored data todetermine the status of patient health. In some embodiments, the healthmanagement system 1000 can also be configured to compare dose deliveredto a patient with a patient medication schedule to monitor compliance.In some embodiments, the health management system can communicate theuser health and dose information to the monitor M through the network1400. The monitor M can analyze user U health data and determine if anychanges to the patient medication plan, for example, insulin and/or anyother medication dosage needs to be made. If a change is required, insome embodiments, the monitor M can communicate any changes to theuser's U medication regimen to the authorized drug dispenser DD. In someembodiments, the monitor M can also communicate this information to thehealth management system 1100 through the network 1400. In someembodiments, the health management system 1100 can update and store theuser U medication regimen and also communicate to the dose measurementsystem 1100, the user U new medication regimen. The user U can thenaccess the dose measurement system 1400 to obtain the new measurementplan, for example, new insulin dosage. In this manner, a diabetic user'sU health can be monitored and managed and the user's U medicationschedule can be dynamically personalized to the user U. In someembodiments, health management system can also communicate the user Uhealth and medication history on a periodic basis. The health andmedication history can be used, for example, to inform the user U of anychanges that need to be made to improve the user's U overall health. Themedication history can also be communicated to the monitor M to analyzethe user's U progressive health.

While various embodiments of the system, methods and devices have beendescribed above, it should be understood that they have been presentedby way of example only, and not limitation. Where methods and stepsdescribed above indicate certain events occurring in certain order,those of ordinary skill in the art having the benefit of this disclosurewould recognize that the ordering of certain steps may be modified andsuch modification are in accordance with the variations of theinvention. Additionally, certain of the steps may be performedconcurrently in a parallel process when possible, as well as performedsequentially as described above. The embodiments have been particularlyshown and described, but it will be understood that various changes inform and details may be made.

For example, although various embodiments have been described as havingparticular features and/or combination of components, other embodimentsare possible having any combination or sub-combination of any featuresand/or components from any of the embodiments described herein. Forexample, although some embodiments were described as having a dosemeasurement system that resembled a pen cap, the dose measurement systemcan also be integrated with a drug delivery device. In some embodiments,vibration and/or ultrasonic waves can be used to generate the signalsignature instead of electromagnetic radiation. In addition, thespecific configurations of the various components can also be varied.For example, the size and specific shape of the various components canbe different than the embodiments shown, while still providing thefunctions as described herein.

The invention claimed is:
 1. A method of estimating a volume of liquidin a drug container, the method comprising: causing a plurality of lightsources to emit electromagnetic radiation toward the drug container;detecting the electromagnetic radiation emitted by at least two of theplurality of light sources; generating a signal signature representativeof the detected electromagnetic radiation; and comparing the signalsignature to a plurality of reference signatures to determine the volumeof liquid in the drug container.
 2. The method of claim 1, furthercomprising: calculating a dose delivered to a patient based on thevolume of liquid in the drug container.
 3. A method, comprising: causinga plurality of light sources to emit electromagnetic radiation toward aninjection pen a first time; detecting the electromagnetic radiationemitted by at least two of the plurality of light sources with aplurality of sensors at the first time; generating a first signalsignature representative of the detected electromagnetic radiation;comparing the first signal signature to a plurality of referencesignatures to determine a first volume of liquid in the injection pen;causing the plurality of light sources to emit electromagnetic radiationtoward the injection pen a second time after the first time; detectingthe electromagnetic radiation emitted by at least two of the pluralityof light sources with the plurality of sensors at the second timegenerating a second signal signature representative of the detectedelectromagnetic radiation; comparing the second signal signature to theplurality of reference signatures to determine a second volume of liquidin the injection pen; and estimating a dose delivered from the injectionpen based on the first volume and the second volume.
 4. The method ofclaim 3, wherein the plurality of light sources and the plurality ofsensors are disposed in an injection pen cap, the method furthercomprising: detecting the first signal signature prior to the injectionpen cap being removed from the injection pen; and detecting the secondsignal signature after the injection pen cap has been placed back on theinjection pen.
 5. The method of claim 1, further comprising: correctingthe signal signature for background light.
 6. The method of claim 5,wherein correcting the signal signature for background light includescomparing the signal signature with a background signature in a darkstate of each of the plurality of light sources.
 7. The method of claim1, further comprising: communicating information associated with thevolume of liquid in the drug container to an external device.
 8. Themethod of claim 1, further comprising: generating the plurality ofreference signatures by recording a signal signature for each of a rangeof dose volumes in the drug container.
 9. The method of claim 1, whereinthe drug container is at least part of a drug delivery device, themethod further comprising: determining, based at least in part on theplurality of reference signatures, at least one of: a coupling or adecoupling of the plurality of light sources to the drug deliverydevice; an attachment or a detachment of an injector to the drugdelivery device; a property of the drug delivery device; and a propertyof a liquid disposed in the drug container.
 10. The method of claim 9,wherein the drug delivery device is an injection pen, the method furthercomprising: determining, based at least in part on the plurality ofreference signatures, at least one of: an attachment or a detachment ofa needle to the injection pen; and a property of the injection pen. 11.The method of claim 3, further comprising: communicating informationassociated with the dose delivered to an external device.
 12. The methodof claim 3, further comprising: generating the plurality of referencesignatures by recording a signal signature for each of a range of dosevolumes in the injection pen.
 13. The method of claim 3, wherein theplurality of light sources and the plurality of sensors are disposed inan injection pen cap removably coupleable to the injection pen.
 14. Amethod of estimating a volume of liquid in a drug container, the methodcomprising: causing a plurality of light sources to emit electromagneticradiation toward the drug container; detecting the electromagneticradiation emitted by at least two of the plurality of light sources;generating a signal signature representative of the detectedelectromagnetic radiation; and comparing the signal signature to aplurality of reference signatures to determine the a property of thedrug container.
 15. The method of claim 14, wherein the property of thedrug container includes a property of a fluid disposed in the drugcontainer.
 16. The method of claim 14, wherein the property of the drugcontainer includes at least one of a refractive index, a color, amarking, and a label.
 17. The method of claim 14, further comprising:generating the plurality of reference signatures by recording a signalsignature for each of a plurality of container types.
 18. The method ofclaim 14, wherein the property of the drug container indicates acontainer type.
 19. The method of claim 14, further comprising:correcting the signal signature for background light.
 20. The method ofclaim 19, wherein correcting the signal signature for background lightincludes comparing the signal signature with a background signature in adark state of each of the plurality of light sources.